Project Description

Gene expression and chemoresistance in tumor cells

Modern gene expression analysis technologies allow the genome-wide identification of differentially expressed genes across diverse cell types and contexts. We use these technologies to characterize gene expression in cancer cells with particular focus on stem cell features and tumor antigens. In addition to the characterization of cancer-specific expression signatures, we are interested in differential gene expression between cancer cells with varying sensitivities to cytotoxic drugs. Putative targets identified by this analysis are further characterized in vitro. These studies largely overlap with our endogenous retrovirus project. Our main cell models for these investigations are Ewing sarcomas and Hodgkin lymphomas.

Our research is currently supported by the Stiftung Mitteldeutsche Kinderkrebsforschung.

Kewitz-Hempel S, Kurch L, Cepelova M, Volkmer I, Sauerbrey A, Conrad E, Knirsch S, Pöpperl G, Steinbach D, Beer AJ, Kramm CM, Sahlmann CO, Erdlenbruch B, Reinbold WD, Odparlik A, Sabri O, Kluge R, Staege MS. Impact of rs12917 MGMT polymorphism on early 18F-FDG-PET response in Pediatric Hodgkin Lymphoma (PHL). Mol Imaging Biol 2019 Apr 3. doi: 10.1007/s11307-019-01350-5. [Epub ahead of print] (2019).

Staege MS. Are EWSR1-FLI positive cell lines from patients with other diagnoses than Ewing sarcoma really Ewing sarcoma cell lines? Pediatr Blood Cancer 22:e27769 (2019).

Braune K, Volkmer I, Staege MS. Characterization of Alstrom syndrome 1 (ALMS1) transcript variants in Hodgkin lymphoma cells. PLoS One 12:e0170694 (2017).

Staege MS. Gene Expression Music Algorithm (GEMusicA)-based characterization of the Ewing sarcoma stem cell signature Stem Cells Int 2016:7674824 (2016).

Bernig T, Ritz S, Brodt G, Volkmer I, Staege MS. Glutathione-S-transferases and chemotherapy Resistance of Hodgkin’s lymphoma cell lines. Anticancer Res 36:3905-3915 (2016).

Kewitz S, Kurch L, Volkmer I, Staege MS. Stimulation of the hypoxia pathway modulates chemotherapy resistance in Hodgkin’s lymphoma cells. Tumor Biol 37:8229-8237 (2016).

Hermes N, Kewitz S, Staege MS. Preferentially expressed antigen in melanoma (PRAME) and the PRAME family of leucine-rich repeat proteins. Curr Cancer Drug Targets 16:400-414 (2016).

Staege MS, Kewitz S, Bernig T, Kühnöl C, Mauz-Körholz C. Prognostic biomarkers for Hodgkin’s lymphoma. Pediatric Hematol Oncol 32:433-454 (2015).

Staege MS. A short treatise concerning a musical approach for the interpretation of gene expression data. Sci Rep 5:15281 (2015).

Staege MS. A multi-component model of Hodgkin’s lymphoma. PLoS One 10:e0124614 (2015).

Staege MS. A paradigm for cybernetics, regulatory circuits and ultra-stability in cancer biology and treatment. Leuk Res 38:1158-1159 (2014).

Bernig T, Richter N, Volkmer I, Staege MS. Functional analysis and molecular characterization of spontaneously outgrown human lymphoblastoid cell lines. Mol Biol Rep 41:6995-7007 (2014).

Sansoni V, Casas-Delucchi CS, Rajan M, Schmidt A, Bönisch C, Thomae AW, Staege MS, Hake SB, Cardoso MC, Imhof A. The histone variant H2A.Bbd is enriched at sites of DNA synthesis. Nucleic Acid Res 42:6405-6420 (2014).

Kewitz S, Stiefel M, Kramm C, Staege MS. Impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression on dacarbazine resistance of Hodgkin’s lymphoma cells. Leuk Res 38:138-143 (2014).

Mahlendorf DE, Staege MS. Characterization of Ewing sarcoma associated cancer/testis antigens. Cancer Biol Ther 14:254-261(2013).

Kewitz S, Volkmer I, Staege MS. Curcumia contra cancer? Curcumin and Hodgkin’s lymphoma. Cancer Growth Metastasis 6:35-52 (2013).

Hesse M, Willscher E, Schmiedel BJ, Posch S, Golbik RP, Staege MS. Sequence and expression of the chicken membrane-associated phospholipases A1 alpha (LIPH) and beta (LIPI). Mol Biol Rep 39:761-769 (2012).

Kewitz S, Bernig T, Staege MS. Histone deacetylase inhibition and gene expression in Hodgkin’s lymphoma. Leuk Res 36:773-778 (2012).

Wernicke CM Richter GHS, Beinvogl BC, Plehm S, Schlitter AM, Bandapalli OR,  Prazeres da Costa O, Hattenhorst UE, Volkmer I, Staege MS, Esposito I, Burdach S, Grunewald TGP. MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival. Leuk Res 36:1185-1192 (2012).

Winkler C, Steingrube DS, Altermann W, Schlaf G, Max D, Kewitz S, Emmer A, Kornhuber M, Banning-Eichenseer U, Staege MS. Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen specific immune responses. Cancer Immunol Immunother 61:1769-1779 (2012).

Li J, Neumann I, Volkmer I, Staege MS. Down-regulation of achaete-scute complex homolog 1 (ASCL1) in neuroblastoma cells induces up-regulation of insulin-like growth factor 2 (IGF2). Mol Biol Rep 38:1515-1521 (2011).

Schmiedel BJ, Hutter C, Hesse M, Staege MS. Expression of multiple membrane-associated phospholipase A1 beta transcript variants and lysophosphatidic acid receptors in Ewing tumor cells. Mol Biol Rep 38:4619-4628 (2011).

Richter GH, Plehm S, Fasan A, Rössler S, Unland R, Bennani-Baiti IM, Hotfilder M, Löwel D, von Luettichau I, Mossbrugger I, Quintanilla-Martinez L, Kovar H, Staege MS, Müller-Tidow C, Burdach S. EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation. Proc Natl Acad Sci U S A 106:5324-5329 (2009).

Burdach S, Plehm S, Unland R, Dirksen U, Borkhardt A, Staege MS, Müller-Tidow C, Richter GH. Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2. Cell Cycle 8:1991-1996 (2009).

Hühn R, Staege MS, Hesse M, Liebig B, Burdach SEG. Cleavage of the tumour-specific EWSR1-FLI1 mRNA by hammerhead ribozymes. Anticancer Res 29:1901-1908 (2009).

Hönnscheidt C, Max D, Richter N, Staege MS. Expression of CD4 on Epstein-Barr virus-immortalized B cells. Scand J Immunol 70:216-225 (2009).

Max D, Hesse M, Volkmer I, Staege MS. High expression of the evolutionarily conserved alpha/beta hydrolase domain containing 6 (ABHD6) in Ewing tumors. Cancer Sci 100:2383-2389 (2009).

Staege MS, Körholz D. New treatment strategies for Hodgkin’s lymphoma. Leuk Res 33:886-888 (2009).

Metzler M, Staege MS, Harder L, Mendelova D, Zuna J, Fronkova E, Meyer C, Flohr T, Bednarova D, Harbott J, Langer T, Gesk S, Trka J, Siebert R, Dingermann T, Marschalek R, Niemeyer C, Rascher W. Inv(11)(q21q23) fuses MLL to the notch co-activator mastermind-like 2 in secondary T-cell acute lymphoblastic leukemia. Leukemia 22:1807-1811 (2008).

Staege MS, Banning-Eichenseer U, Weissflog G, Volkmer I, Burdach S, Richter G, Mauz-Körholz C, Föll J, Körholz D. Gene expression profiles of Hodgkin’s lymphoma cell lines with different sensitivity to cytotoxic drugs. Exp Hematol 36:886-896 (2008).

Föll JL, Hesse M, Volkmer I, Schmiedel BJ, Neumann I, Staege MS. Membrane-associated phospholipase A1 beta (LIPI) is an Ewing tumour-associated cancer/testis antigen. Pediatr Blood Cancer 51:228-234 (2008).

Föll JL, Max D, Giersberg C, Körholz D, Staege MS. Sensitivity of Hodgkin’s lymphoma cell lines to the cell cycle inhibitor roscovitine. Anticancer Res 28:887-894 (2008).

Föll JL, Volkmer I, Giersberg C, Kornhuber M, Horneff G, Staege MS. Loss of detectability of Charcot-Leyden crystal protein transcripts in blood cells after treatment with dimethyl sulfoxide. J Immunol Methods 339:99-103 (2008).

Berg T, Fliegauf M, Burger J, Staege MS, Liu S, Martinez N, Heidenreich O, Burdach S, Haferlach T, Werner MH, Lübbert M. Transcriptional upregulation of p21/WAF/Cip1 in myeloid leukemic blasts expressing AML1-ETO. Haematologica 93:1728-1733 (2008).

Staege MS, Hansen G, Baersch G, Burdach S. Molecular and functional characterization of interleukin-2 transgenic Ewing tumor cells for in vivo immunotherapy. Pediatr Blood Cancer 43:23-34 (2004).

Staege MS, Hutter C, Neumann I, Foja S, Hattenhorst UE, Hansen G, Afar D, Burdach SE. DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. Cancer Res 64:8213-8221 (2004).